恶性肿瘤患者血栓分子标志物的临床评价

目的探讨血栓分子标志物在恶性肿瘤患者血栓形成的早期诊断价值,并对恶性肿瘤患者形成血栓危险因素进行评价。方法诊断性研究。选取2017年9月至2019年2月牡丹江医学院附属红旗医院及牡丹江市肿瘤医院的恶性肿瘤患者,共1366例包括肺癌、乳腺癌及结直肠癌,男562例,女804例,年龄(59.45±15.10)岁],对照组为70名健康体检人群男35名,女35名,年龄(50.41±18.90)岁],其中形成静脉血栓69例,男32例,女37例,平均年龄(61.20±15.71)岁。采用化学发光免疫分析法检测其静脉血浆中的血栓调节蛋白(TM)、凝血酶-抗凝血酶复合物(TAT)、组织型纤溶酶原激活物/抑制剂-1复合物(t-PAIC)、纤溶酶-抗纤溶酶复合物(PIC)。根据各项标志物的敏感度及特异度,采用受试者工作特征曲线评价各项标志物的诊断性能,采用Cox回归分析进行单因素及多因素风险分析。结果不同类型的恶性肿瘤患者静脉血栓栓塞(VTE)发生率具有统计学差异,肺癌最高,其次为结直肠癌及乳腺癌(P<0.05);肺癌、乳腺癌及结直肠癌血栓组的TM、TAT、t-PAIC及PIC水平高于对照组,非血栓组的TAT、t-PAIC及PIC水平均高于对照组,差异均具有统计学意义(均P<0.05)。TM的最佳截断水平为10.57 IU/ml(敏感度为50.30%,特异度75.50%,AUC=0.671),TAT的最佳截断水平为4.16 ng/ml(敏感度为80.30%,特异度为62.80%,AUC=0.757),t-PAIC的最佳截断水平为11.44 ng/ml(敏感度为52.50%,特异度为84.00%,AUC=0.682),PIC的最佳截断水平为1.18μg/ml(敏感度为67.20%,特异度为79.50%,AUC=0.790),四项分子标志物联合检测敏感度最佳,诊断性能最好(86.90%,AUC=0.807)。年龄、分期、转移、手术、肿瘤直径及PIC水平是影响恶性肿瘤VTE发生的独立影响因素(均P<0.05)。结论不同类型的恶性肿瘤血栓发生率不同,TM、TAT、t-PAIC及PIC联合检测诊断性能最好,可作为恶性肿瘤发生VTE的新型筛查方法。年龄、分期、转移、手术及肿瘤直径是恶性肿瘤发生VTE的高危因素,PIC水平可作为恶性肿瘤患者6个月内并发VTE风险的可靠标志物。

Clinical evaluation of thrombus molecular markers in patients with malignant tumor

Objective To explore the early diagnostic value of thrombus molecular markers in thrombosis ofpatients with malignant tumors and to evaluate their risk factors.Methods Diagnostic research.A total of 1366 patients(including lung cancer,breast cancer and colorectal cancer,)were randomly selected in the Red Flag Hospital of Mudanjiang Medical College and Mudanjiang Cancer Hospitalfrom September 2009 to February 1919.Among them,562 were males and 804 were females with average age(59.45±15.10)years old.The control group consisted of 70healthy donors(35 males and 35 females,with an average age of(49.60±19.12)years old),including 69 cases of venous thrombosis(thrombotic group,32 males and37 females,with an average age of(61.20±15.71)years old).Chemoluminescent enzyme immunoassay was used to detect thromboregulatory proteins(TM),thrombin-antithrombin complexes(TAT),tissue plasminogen activators/inhibitors-1 complexes(t-PAIC),plasminase-anti-fibrinolysis complexes(PIC)in venous plasma.According to the sensitivity and specificity of each marker,the receiver′s work characteristic curve was drawn to evaluate its diagnostic performance.Cox regression analysis was used for single-factor and multi-factor risk analysis.Results The incidence of venous thromboembolism(VTE)in patients with different types of malignant tumors was statistically significant,with lung cancer being the highest,followed by colorectal cancer and breast cancer(P<0.05).The levels of TM,TAT,t-PAIC and PIC were significantly higher in the lung,breast and colorectal thrombosis group than in the control group.The differences were statistically significant(all P<0.05).The optimal cut-off level for TM is 10.57 IU/ml(sensitivity 50.30%,specificity 75.50%,AUC=0.671),and the optimal cut-off level for TAT is 4.16 ng/ml(sensitivity is 80.30%,specificity is 62.80%,AUC=0.757).The optimal truncation level for t-PAIC is 11.44 ng/ml(sensitivity 52.50%,specificity 84.00%,AUC=0.682),and the optimal truncation level for PIC is 1.18μg/ml(sensitivity 67.20%,specificity is 79.50%,AUC=0.790).The combined detection of the four molecular markers has the best sensitivity and diagnostic performance(86.90%,AUC=0.807).Age,stage,metastasis,surgery,tumor diameter,and PIC levels are independent factors that affect the occurrence of VTE in malignant tumors(all P<0.05).Conclusions Different types of malignant tumors have different rates of thrombosis.The combined detection ofTM,TAT,t-PAIC and PIC have the best diagnostic performance,and can be used as a new early diagnosis method for VTE in malignant tumors.Age,stage,metastasis,surgery,and tumor diameter are risk factors for VTE in malignant tumors.PIC levels can be used as a reliable markerfor the risk of VTE in patients with malignant tumors within 6 months.